Induced miR-31 by 5-fluorouracil exposure contributes to the resistance in colorectal tumors

Yoshihito Nakagawa, Yuki Kuranaga, Tomomitsu Tahara, Hiromi Yamashita, Tomoyuki Shibata, Mitsuo Nagasaka, Kohei Funasaka, Naoki Ohmiya, Yukihiro Akao

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3 Citations (Scopus)

Abstract

Drug resistance makes treatment difficult in cancers. The present study identifies and analyzes drug resistance-related miRNA in colorectal cancer. We established 4 types of 5-fluorouracil (5-FU)-resistant colon cancer cell lines in vitro and in vivo. We then analyzed the miRNA expression profile by miRNA array in these 4 cell lines, and identified the drug resistance-related miRNAs. We examined the expression levels of the identified miRNA in 112 colorectal tumor samples from the patients. We identified 12 possible miRNAs involved in 5-FU resistance by miRNA arrays. We then examined the relationship between miR-31, which was the most promising among them, and drug resistance. The ectopic expression of mimic miR-31 showed significant 5-FU resistance in the parental DLD-1 cells, while anti–miR-31 caused significant growth inhibition in DLD/F cells; that is, 5-FU-resistant colon cancer cell line DLD-1 under exposure to 5-FU. When we exposed high doses of 5-FU to parent or 5-FU-resistant cells, the expression levels of miR-31 were raised higher than those of controls. Notably, the expression levels of miR-31 were positively correlated with the grade of clinical stages of colorectal tumors. The protein expression levels of factors inhibiting hypoxia-inducible factor 1 were downregulated by transfection of mimic miR-31 into DLD-1 cells. This study provides evidence supporting the association of miR-31 with 5-FU drug resistance and clinical stages of colorectal tumors.

Original languageEnglish
Pages (from-to)2540-2548
Number of pages9
JournalCancer science
Volume110
Issue number8
DOIs
Publication statusPublished - 01-01-2019

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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  • Cite this

    Nakagawa, Y., Kuranaga, Y., Tahara, T., Yamashita, H., Shibata, T., Nagasaka, M., Funasaka, K., Ohmiya, N., & Akao, Y. (2019). Induced miR-31 by 5-fluorouracil exposure contributes to the resistance in colorectal tumors. Cancer science, 110(8), 2540-2548. https://doi.org/10.1111/cas.14090